Diabetes mellitus in man may have several etiologies. The pathogenetic factors responsible for the juvenile and maturity-onset forms of the disease doubtless differ. Studies designed to elucidate the causation of diabetes in man have thus far failed to yield conclusive evidence. Genetic influences appear to play a role in most forms of the disease; immunologic factors and viruses may contribute to the pathogenesis of juvenile-onset diabetes. Animal models would permit detailed investigations of possible etiologic considerations and possible pathogenetic mechanisms for this important disease. The encephalomyocarditis virus causes a diabetes-like disease in mice by injuring beta cells in the islets of Langerhans. The factors influencing the susceptibility of these cells to the virus will be investigated in this project. Additional viruses that have beta cell tropism (cytomegalovirus and reoviruses) also will be studied. Since immunological factors may play a role in diabetes in man, we will explore the effects of viruses on the immunologic responses of animals. Both humoral and cell-mediated immune mechanisms directed against the beta cell will be examined.